A pilot study of adjunctive atomoxetine treatment to second-generation antipsychotics for cognitive impairment in schizophrenia
A pilot study of adjunctive atomoxetine treatment to second-generation antipsychotics for cognitive impairment in schizophrenia
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DOI：
10.1097/jcp.0b013e318161318f
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发表时间：
2008-02-01
影响因子：
2.9
通讯作者：
Harvey, Philip D.
中科院分区：
文献类型：
--
作者：
Friedman, Joseph I.;Carpenter, David;Harvey, Philip D.
前额皮质多巴胺和去甲肾上腺素的改变与精神分裂症的一些认知障碍之间的关系支持了一种通过控制前额皮质多巴胺和去甲肾上腺素对认知症状进行药理学补救的方法。阿托莫西汀是一种选择性去甲肾上腺素再摄取抑制剂，可引起大脑去甲肾上腺素的广泛增加和前额叶多巴胺的继发性和选择性增加。鉴于此，我们在一项针对精神分裂症患者的安慰剂对照试验中评估了托莫西汀的认知效果。此外，进行了功能性磁共振成像调查，以评估托莫西汀认知影响的神经机制。20名精神分裂症患者随机接受安慰剂或阿托西汀80mg /天的治疗，进行为期8周的平行设计治疗试验。用《精神分裂症患者认知能力简要评估》评估认知表现。托莫西汀治疗没有显著的认知改善。然而，托莫西汀治疗与左背外侧前额叶和左后扣带皮层的工作记忆相关激活显著增加相关。本研究的阴性结果与安非他明增强精神分裂症患者认知能力的有效性相冲突，可能与安非他明产生的皮层激活和失活的不同模式有关。
Relationships between altered prefrontal cortical dopamine, norepinephrine, and some of the cognitive impairments of schizophrenia support an approach for pharmacological remediation of cognitive symptoms through manipulations of prefrontal cortical dopamine and norepinephrine. Atomoxetine, a selective norepinephrine reuptake inhibitor, produces a widespread increase in brain norepinephrine and a secondary and selective increase in prefrontal dopamine. Given this, we evaluated atomoxetine's cognitive effects in a pilot placebo-controlled trial in patients with schizophrenia. Moreover, a functional magnetic resonance imaging investigation was undertaken to assess the neural mechanisms underlying the cognitive effects of atomoxetine. Twenty participants with schizophrenia were randomized to treatment with placebo or atomoxetine 80 mg daily for an 8-week parallel-designed treatment trial. Cognitive performance was assessed with the Brief Assessment of Cognition in Schizophrenia. No significant cognitive improvement was associated with atomoxetine treatment. However, atomoxetine treatment was associated with significantly greater increases in working memory-related activation of the left dorsolateral prefrontal and left posterior cingulate cortices. The negative results of this study conflict with the effectiveness of amphetamine in enhancing the cognitive abilities of schizophrenic patients and may be related to the differential pattern of cortical activation and deactivation produced by amphetamine.